Yamada, Eijiro, Bastie, Claire C., Koga, Hiroshi, Wang, Yichen, Cuervo, Ana Maria and Pessin, Jeffrey E.. (2012) Mouse skeletal muscle fiber-type-specific macroautophagy and muscle wasting are regulated by a Fyn/STAT3/Vps34 signaling pathway. Cell Reports, Vol.1 (No.5). pp. 557-569. ISSN 22111247

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Abstract

Skeletal muscle atrophy induced by aging (sarcopenia), inactivity, and prolonged fasting states (starvation) is predominantly restricted to glycolytic type II muscle fibers and typical spares oxidative type I fibers. However, the mechanisms accounting for muscle fiber-type specificity of atrophy have remained enigmatic. In the current study, although the Fyn tyrosine kinase activated the mTORC1 signaling complex, it also induced marked atrophy of glycolytic fibers with relatively less effect on oxidative muscle fibers. This was due to inhibition of macroautophagy via an mTORC1-independent but STAT3-dependent reduction in Vps34 protein levels and decreased Vps34/p150/Beclin1/Atg14 complex 1. Physiologically, in the fed state endogenous Fyn kinase activity was increased in glycolytic but not oxidative skeletal muscle. In parallel, Y705-STAT3 phosphorylation increased with decreased Vps34 protein levels. Moreover, fed/starved regulation of Y705-STAT3 phosphorylation and Vps34 protein levels was prevented in skeletal muscle of Fyn null mice. These data demonstrate a Fyn/STAT3/Vps34 pathway that is responsible for fiber-type-specific regulation of macroautophagy and skeletal muscle atrophy.

Item Type:	Journal Article
Subjects:	Q Science > QL Zoology
Divisions:	Faculty of Medicine > Warwick Medical School > Metabolic and Vascular Health
Library of Congress Subject Headings (LCSH):	Muscular atrophy, Mice -- Physiology, Cellular control mechanisms
Journal or Publication Title:	Cell Reports
Publisher:	Cell Press
ISSN:	22111247
Date:	3 May 2012
Volume:	Vol.1
Number:	No.5
Page Range:	pp. 557-569
Identification Number:	10.1016/j.celrep.2012.03.014
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	National Institutes of Health (U.S.) (NIH)
Grant number:	DK033823 (NIH), DK082694 (NIH), DK020541 (NIH)
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URI:	http://wrap.warwick.ac.uk/id/eprint/48058

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